不同剂量尼古丁对成年大鼠阴茎海绵体内源性CO含量及NOS活性影响的研究

Effect of different doses nicotine on the endogenous carbon monoxide level and nitile oxide synthase activity of the adult rat corpus cavernosum

目的探讨不同剂量尼古丁对成年雄性大鼠阴茎勃起功能及阴茎海绵体内源性一氧化碳(CO)含量及一氧化氮合酶(NOS)活性的影响。方法将32只12周龄雄性大鼠随机分为4组,对照组、尼古丁(0.5mg·kg-1·d-1)组、尼古丁(1.5mg·kg-1·d-1)组、尼古丁(2.5mg·kg-1·d-1)组。给药方式采用皮下注射。8周后,阿朴吗啡试验观察大鼠阴茎勃起情况。取阴茎海绵体,用改良双波长分光光度法测量其CO浓度。应用改良的Griess法测量其NOS活性。结果与对照组比较,尼古丁各组阴茎勃起次数、CO含量及NOS活性明显减少(P<0.01)。阴茎勃起次数,尼古丁(2.5mg·kg-1·d-1)组较尼古丁(0.5mg·kg-1·d-1)组明显减少(P<0.01),尼古丁(1.5mg·kg-1·d-1)组较尼古丁(0.5mg·kg-1·d-1)组、尼古丁(2.5mg·kg-1·d-1)组较尼古丁(1.5mg·kg-1·d-1)组减少(P>0.05)。尼古丁给药剂量越大,CO含量及NOS活性越低,尼古丁注射各组间两两比较,差异有统计学意义(P<0.01)。结论尼古丁可导致成年雄性大鼠阴茎勃起功能减弱,阴茎海绵体内源性CO含量及NOS活性下降;其影响呈给药剂量依赖性;表明内源性CO是尼古丁致阴茎勃起功能障碍(ED)的重要信使分子,尼古丁可能通过降低内源性CO含量及NOS活性致ED。

Objective To investigate the effect of different doses nicotine on erectile function,the endogenous carbon monoxide（CO） level and nitile oxide synthase（NOS） activity of the adult male rat corpus cavernosum.Methods 32 12-week-old male rats were randomly divided into four groups：control group,nicotine（0.5 mg·kg^-1·d^-1group,nicotine（1.5 mg·kg^-1·d^-1roup and nicotin（2.5 mg·kg^-1·d^-1roup.Drug delivery by using subcutaneous injection.Eight weeks later,apomorphine test erection function of rats.Corpus cavernosum was drawed.CO level was detected by an improved two-wavelength spectrophotometry.NOS activity was detected by an improved Griess.Results Compared with control group,the number of penile erection,endogenous CO content and NOS activity of the nicotine injection group rats were significantly decreased（P〈0.01）.The number of penile erection s,nicotin（2.5 mg·kg^-1·d^-1roup compared with nicotine（0.5 mg·kg^-1·d^-1group was significantly reduced（P〈0.01）,nicotine（1.5 mg·kg^-1·d^-1roup compared with nicotine（0.5 mg·kg^-1·d^-1group and nicotine（1.5 mg·kg^-1·d^-1roup compared with nicotine（0.5 mg·kg^-1·d^-1group reduced（P〉0.05）.The greater the dose of nicotine was,the lower levels of endogenous CO and NOS activity was.The difference between the two nicotine groups was significant（P〈0.01）.Conclusion Nicotine can lead to adult male rats erectile dysfunction,and reduced levels of endogenous CO and NOS activity in corpus cavernosum penis;its effects are dose-dependent manner,indicating that endogenous CO is an important messenger molecule on nicotine-induced erectile dysfunction,and nicotine possibly caused erectile dysfunction by reducing endogenous CO and NOS activity.